Compact enhanced yield blood processing systems

ABSTRACT

A chamber for use in a rotating field to separate blood components is described. An inlet port near one end of the chamber introduces blood into the chamber for flow circumferentially about the rotational axis toward the opposite end of the chamber for separation into at least one blood component. At least one outlet port is juxtaposed next to the inlet port near the one end of the chamber for conveying one separated blood component from the channel. The chamber directs the one separated blood component to a collection region near the opposite end of the chamber. An enclosed interior collection passage within the channel leads from the collection region and directs the one collected component to the outlet port for transport from the chamber.

RELATED APPLICATIONS

This application is a Division of application Ser. No. 08/856,096 filedMay 14, 1997, U.S. Pat. No. 6,228,017 which is a Division of applicationSer. No. 08/146,403 filed Nov. 1, 1993, U.S. Pat. No. 5,656,163, whichis a continuation of application Ser. No. 07/964,771 filed Oct. 22,1992, abandoned, which is a continuation-in-part of U.S. patentapplication Ser. No. 07/814,403 entitled “Centrifuge with Separable Bowland Spool Elements Providing Access to the Separation Chamber,” filedDec. 23, 1991, abandoned, which is also a continuation-in-part of U.S.patent application Ser. No. 07/748,244 entitled “Centrifugation PheresisSystem,” filed Aug. 21, 1991, U.S. Pat. No. 5,322,620, which is itself acontinuation of U.S. patent application Ser. No. 07/514,995, filed May26, 1989, U.S. Pat. No. 5,104,526 which is itself a continuation of U.S.patent application Ser. No. 07/009,179, filed Jan. 30, 1987 (now U.S.Pat. No. 4,834,890).

FIELD OF THE INVENTION

The invention relates to centrifugal processing systems and apparatus.

BACKGROUND OF THE INVENTION

Today blood collection organizations routinely separate whole blood bycentrifugation into its various therapeutic components, such as redblood cells, platelets, and plasma.

Conventional blood processing systems and methods use durable centrifugeequipment in association with single use, sterile processing chambers,typically made of plastic. The centrifuge equipment introduces wholeblood into these chambers while rotating them to create a centrifugalfield.

Whole blood separates within the rotating chamber under the influence ofthe centrifugal field into higher density red blood cells andplatelet-rich plasma. An intermediate layer of white blood cells andlymphocytes forms an interface between the red blood cells andplatelet-rich plasma.

Conventional blood processing methods use durable centrifuge equipmentin association with single use, sterile processing systems, typicallymade of plastic. The operator loads the disposable systems upon thecentrifuge before processing and removes them afterwards.

Conventional centrifuges often do not permit easy access to the areaswhere the disposable systems reside during use. As a result, loading andunloading operations can be time consuming and tedious.

Disposable systems are often preformed into desired shapes to simplifythe loading and unloading process. However, this approach is oftencounterproductive, as it increases the cost of the disposables.

SUMMARY OF THE INVENTION

The invention provides improved blood processing systems and methodsthat create unique dynamic flow conditions within a compact, easilyhandled processing chamber.

One aspect of the invention provides a chamber for use in a rotatingfield to separate blood components. The chamber includes a separationchannel having a low-G side wall radially spaced from the rotationalaxis, a high-G side wall radially spaced from the rotational axisfarther than the low-G side wall, and end walls that are spaced apartcircumferentially about the rotation axis. An inlet port near the firstend wall introduces blood into the channel for flow circumferentiallyabout the rotational axis from the first end wall toward the second endwall for separation into at least one blood components.

In this aspect of the invention, at least one outlet port is juxtaposednext to the inlet port near the first end wall for conveying oneseparated blood component from the channel. In this way, the fluid flowtubing associated with the chamber is located within a single compactregion of the chamber. This simplifies handling of the chamber,particularly when loading and unloading the chamber in a processingcentrifuge.

The compact chamber that embodies the features of the invention directsone separated blood component to a collection region near the second endwall. An enclosed interior collection passage within the channel thatleads from the collection region and directs the one collected componentto the outlet port for transport from the chamber.

In a preferred embodiment, the chamber includes a barrier surface nearthe second end wall for creating a restricted inlet between thecollection region and the collection passage.

Another aspect of the invention provides a chamber defining a separationzone that is divided into contiguous first and second separationchannels.

In the arrangement, each channel includes an inlet port near itsassociated first end wall for introducing blood into the channel forflow circumferentially about the rotational axis from the first end walltoward the second end wall for separation. Each channel also includes atleast one outlet port juxtaposed its associated inlet port for conveyinga separated blood constituent from the associated channel.

Thus, according to the invention, the inlet and outlet ports of the twoseparation channels are mutually juxtaposed in a compact region on thechamber.

The invention may be embodied in several forms without departing fromits spirit or essential characteristics. The scope of the invention isdefined in the appended claims, rather than in the specific descriptionpreceding them. All embodiments that fall within the meaning and rangeof equivalency of the claims are therefore intended to be embraced bythe claims.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a diagrammatic view of an enhanced yield axial flow processingchamber that embodies the features of the invention;

FIG. 2 is a diagrammatic view of the chamber shown in FIG. 1 operatingin a centrifugation field;

FIG. 3 is a diagrammatic view of the interior of the chamber shown inFIG. 1 when processing whole blood within the centrifugation field;

FIG. 3A is a graph showing the distribution of increasing regions ofsurface hematocrit along the interface formed in a blood separationchamber;

FIGS. 4 and 5 are diagrammatic views of prior art axial flow bloodprocessing chambers;

FIGS. 6A and 6B are a perspective views of a blood processing assemblythat incorporates enhanced yield first and second stage axial flowprocessing chambers, each with an associated centrifuge holder shown inan opened position, with FIG. 6A showing the first stage holder and 6Bshowing the second stage holder;

FIG. 7A is a top view of the blood processing assembly shown in FIG. 6in position in a centrifuge;

FIG. 7B is a schematic view of the flow system associated with the bloodprocessing assembly when being used to separate blood components;

FIG. 8 is a perspective view of the first stage centrifuge holderassociated with the assembly shown in FIG. 6A, when closed;

FIG. 9A is a plan view of the high-G surface of the first stage holdershown in FIG. 6A;

FIG. 9B is a plan view of the low-G surface of the first stage holdershown in FIG. 6A;

FIG. 10A is a perspective view of the high-G surface of the second stageholder shown in FIG. 6B;

FIG. 10B is a plan view of the contours of the second stagecentrifugation chamber, when in its operative position in the centrifugeholder;

FIG. 11 is a diagrammatic view of an enhanced yield circumferential flowprocessing chamber that embodies the features of the invention;

FIG. 12 is a diagrammatic view of the chamber shown in FIG. 11 operatingin a centrifugation field;

FIG. 13 is a diagrammatic view of the interior of the chamber shown inFIG. 11 when processing whole blood within the centrifugation field;

FIGS. 14 and 15 are diagrammatic views of prior art circumferential flowblood processing chambers;

FIG. 16 is a plan view of a blood processing assembly that incorporatesan enhanced yield circumferential flow processing chamber that embodiesthe features of the invention;

FIG. 17 is a view of the interior of the blood processing assembly shownin FIG. 16, taken between the low-G and high-G walls radially along thecentrifugation field;

FIG. 18 is a plan view of an alternative blood processing assembly thatincorporates an enhanced yield circumferential flow processing chamberthat embodies the features of the invention;

FIG. 19 is a view of the interior of the blood processing assembly shownin FIG. 18, taken between the low-G and high-G walls radially along thecentrifugation field;

FIG. 20 is a side view of a centrifuge that can be used in associationwith either one of the blood processing assemblies shown in FIGS. 16/17or 18/19, showing the bowl and spool assemblies in their upraised andseparated position;

FIG. 21 is a side view of the centrifuge shown in FIG. 20, showing thebowl and spool assemblies in their suspended and operating position;

FIG. 22 is an enlarged perspective view of one of the blood processingassemblies shown in FIGS. 16/17 or 18/19 being wrapped for use about thespool of the centrifuge shown in FIG. 20;

FIG. 23 is an enlarged perspective view, with portions broken away, ofone of the blood processing assemblies shown in FIGS. 16/17 or 18/19mounted for use on the bowl and spool assemblies of the centrifuge shownin FIG. 20;

FIG. 24 is a top interior section view, taken generally along line 24—24in FIG. 23, of the processing chamber formed by the bowl and spoolassemblies of the centrifuge shown in FIG. 20;

FIGS. 25A/B/C are enlarged perspective views of an interior ramp used inassociation with either one of the blood processing assemblies shown inFIGS. 16/17 or 18/19 for controlling flow of PRP from the chosenassembly;

FIG. 26 is a view of the vortex conditions generated within the bloodprocessing assembly shown in FIGS. 16/17 during use;

FIG. 27 is a single needle platelet collection system that can be usedin association with either one of the blood processing assemblies shownin FIGS. 16/17 or 18/19;

FIG. 28 is a double needle platelet collection system that can be usedin association with either one of the blood processing assemblies shownin FIGS. 16/17 or 18/19;

FIG. 29 is a plasma recirculation control system that can be used inassociation with either one of the blood processing systems shown inFIG. 27 or 28;

FIG. 30 is a perspective view, with portions broken away and in section,of an interface control system mounted on the rotating (one omega)portion of the centrifuge shown in FIGS. 20 and 21 and used inassociation with the ramp shown in FIG. 25;

FIG. 31A is an enlarged perspective view of the rotating interfaceviewing head associated with the interface control system shown in FIG.30;

FIG. 31B is a side section view showing the interior of rotatinginterface viewing head shown in FIG. 31A;

FIG. 32 is a schematic view of the light intensity control circuitassociated with the interface control system shown in FIG. 30;

FIGS. 33A/B/C are a series of diagrammatic views showing the operationof the interface control system shown in FIG. 30 during rotation of thecentrifuge assembly;

FIGS. 34A/B are flow charts showing the operation of the interfacecontrol circuit associated with the interface control system shown inFIG. 30;

FIGS. 35A/B show, respectively, the platelet counts and mean plateletvolumes sampled during a 45 minute procedure using a separation chamberthat embodies the features of the invention; and

FIGS. 36A/B show, respectively, the platelet counts and mean plateletvolumes sampled during a 45 minute procedure using another separationchamber than embodies the features of the invention.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

I. Enhanced Yield Axial Flow Systems

A. Single Stage Whole Blood Separation Systems

FIGS. 1 to 3 show, in diagrammatic fashion, a single stage axial flowcentrifugal blood processing system. The system includes a chamber 10that embodies the features of the invention.

In use, the system separates whole blood within the chamber 10 into redblood cells (RBC) and plasma rich in platelets (called platelet-richplasma, or PRP). This specification and drawings will identify red bloodcells as RBC; platelet-rich plasma as PRP; and whole blood as WB.

The system includes a holder 12 that rotates the chamber 10 about anaxis 14 (see FIG. 2), to thereby create a centrifugal field within thechamber 10. The centrifugal field extends from the rotational axis 14radially through the chamber 10.

As FIG. 3 shows, the chamber wall 16 closest to the rotational axis 14will be subject to a lower centrifugal force (or G-force) than thechamber wall 18 farthest away from the rotational axis 14. Consequently,the closer chamber wall 16 will be called the low-G wall, and thefarthest chamber wall 18 will be called the high-G wall.

While rotating, the chamber 10 receives WB through a first port 20. TheWB follows an axial flow path in the chamber 10. That is, it flows in apath that is generally parallel to the rotational axis 14 (as FIG. 2best shows). Consequently, the chamber 10 will be called an axial flowblood processing chamber.

In the geometry shown in FIGS. 1 and 2, the transverse top and bottomedges of the axial flow chamber 10 (which lie across the axial flowpath) are shorter than the longitudinal side edges (which lie along theaxial flow path). Still, alternative geometries are possible. Forexample, the transverse top and bottom edges can extend 360 degrees toform a bowl, the outer periphery of which constitutes an axial flowchamber.

WB separates within the chamber 10 under the influence of thecentrifugal field into RBC and PRP. As FIG. 3 shows, the higher densityRBC move toward the high-G wall 18, displacing the lighter density PRPtoward the low-G wall 16. A-second port 22 draws the RBC from thechamber 10 for collection. A third port 24 draws the PRP from thechamber 10 for collection.

An intermediate layer called the interface 26 forms between the RBC andPRP. The interface 26 constitutes the transition between the formedcellular blood components and the liquid plasma component. Large amountsof white blood cells and lymphocytes populate the interface 26.

Platelets, too, can leave the PRP and settle on the interface 26. Thissettling action occurs when the radial velocity of the plasma near theinterface 26 is not enough to keep the platelets suspended in the PRP.Lacking sufficient radial flow of plasma, the platelets fall back andsettle on the interface 26.

One aspect of the invention establishes flow conditions within thechamber 10 to “elute” platelets from the interface 26. The elution liftsplatelets from the interface 26 and into suspension in the PRP.

To establish beneficial elution conditions within the chamber 10, thePRP collection port 24 and the WB inlet port 20 are juxtaposed so thatthe PRP exits the chamber 10 in the same region where WB enters thechamber 10.

The illustrated embodiment, as shown in FIG. 1, locates the PRPcollection port 24 on the same transverse edge of the chamber 10 as theWB inlet port 20. In FIGS. 1 to 3, this transverse edge is locatedphysically at the top of the chamber 10.

The invention also arranges the RBC collection port 22 and the PRPcollection port 24 so that PRP exits the chamber 10 in a region oppositeto the region where RBC exit the chamber 10, relative to the axial flowof WB in the chamber 10.

The illustrated embodiment, as FIG. 1 shows, locates the RBC collectionport 22 on the transverse edge that is opposite to transverse edge wherethe WB inlet and PRP collection ports 20 and 24 are located. In FIGS. 1to 3, this transverse edge is located physically at the bottom of thechamber 10.

It should be appreciated that the centrifugal field is not sensitive to“top” and “bottom” port placement. The particular “top edge” and “bottomedge” relationship of the ports 20; 22; and 24 shown in FIGS. 1 to 3could be reversed, placing the WB inlet and PRP collection ports 20 and24 on the bottom edge and the RBC collection port 22 on the top edge.

The chamber 10 shown in FIGS. 1 to 3 differs significantly from prioraxial flow blood separation chambers 10A and 10B, which FIGS. 4 and 5show. As there shown, the prior chambers 10A and 10B do not place thePRP collection port 24 and the WB inlet port on the same transverse edgeof the chamber. Instead, the prior chambers 10A and 10B purposelyseparate these ports 20 and 24 on different edges of the chamber.

In the prior chamber 10A shown in FIG. 4, the PRP collection port 24 andthe WB inlet port 20 occupy opposite transverse edges of the chamber. InFIG. 4, the PRP collection port 24 occupies the top transverse edge, andthe WB inlet port 20 occupies the bottom transverse edge. In thisconstruction, there are two RBC collection ports 22, which occupy thesame transverse edge as the PRP collection port 24 and which aY-connector joins. This port arrangement is shown in Cullis U.S. Pat.No. 4,146,172.

In the prior chamber 10B shown in FIG. 5, the PRP collection port 24occupies a transverse (top) edge of the chamber, while the WB inlet port20 occupies a longitudinal (side) edge. In this construction, the RBCcollection port 22 occupies an opposite (bottom) transverse edge of thechamber. This arrangement locates the WB inlet port 20 between the PRPcollection port 24 and the RBC collection port 22.

To further enhance the platelet elution conditions within the chamber10, the distance between the low-G wall 16 and the interface 26 ispreferably smaller in the region of the RBC collection port 22 than inthe region of the PRP collection port 24. The illustrated embodiment(see FIG. 3) achieves this result by uniformly tapering the low-G wall16 toward the high-G wall 18 between the PRP collection port 24 and theRBC collection port 22. FIG. 3 shows the tapering low-G wall 16 inphantom lines.

The same result can be obtained without continuously or uniformlytapering the low-G wall 16 along the entire length of the axial flowpath between the PRP collection port 24 and the RBC collection port 22.The low-G wall 16 can begin its taper farther away from the PRPcollection port 24 than FIG. 3 shows, closer to the region of the RBCcollection port 22.

The axial flow processing chamber 10 configured according to this aspectof the invention serves to increase platelet yields due to the interplayof two principal dynamic flow conditions, one radial and the other axialin direction.

First, due to the juxtaposition of the WB inlet port 20 and the PRPcollection port 24, the chamber 10 produces a dynamic radial plasma flowcondition near the PRP collection port 24. The radial flow condition isgenerally aligned along the centrifugal force field. The radial plasmaflow condition continuously elutes platelets off the interface 26 intothe PRP flow next to the PRP collection port 24.

Second, by narrowing the gap between the low-G wall 16 and the interface26 next to the RBC collection port 22, compared to the gap next to thePRP collection port 24, the chamber 10 produces a dynamic axial plasmaflow condition between the two ports 22 and 24. The axial flow conditionis generally transverse the centrifugal force field. The axial plasmaflow condition continuously drags the interface 26 back towards the PRPcollection port 24, where the higher radial plasma flow conditions existto sweep the platelets off the interface 26.

FIG. 3 diagrammatically shows the enhanced platelet separation effectdue to these complementary radial and axial flow conditions.

WB enters the chamber 10 at a given entry hematocrit, which indicatesthe volume of RBC per unit volume of WB. A typical healthy donor has apredonation hematocrit of about 42.5%.

The hematocrit of the blood lying on the boundary between the RBC andplasma along the interface 26 (called the surface hematocrit) remains ator substantially the same as the entry hematocrit in the entry regionR_(e) of the chamber 10 near the WB inlet port 20. FIG. 3A shows thisentry region R_(e) as lying to the left of the 0.40 surface hematocritisoconcentration line (which is the same as the entry 40% hematocrit).

The size of the entry region R_(e) varies according to the hematocrit ofthe blood entering the chamber 10. For a given chamber configuration,the lower the entry hematocrit is, the smaller the entry region R_(e)becomes.

The size of the entry region R_(e) also depends upon the strength of thecentrifugal field within the chamber and the surface area of thechamber.

As FIG. 3A shows, the surface hematocrit successively increases aboveits entry level outside the entry region R_(e) along the length of thechamber 10 toward the terminal region R₁, where separation is halted.This is because more red blood cells separate and collect toward thehigh-G wall 18 along the length of the chamber 10.

FIG. 3A shows the increasing surface hematocrit along the interface 26as intersected by isoconcentration lines 0.6 (representing a 60% surfacehematocrit) to 0.9 (representing a 90% surface hematocrit).

Further details of the distribution of RBC during centrifugation in achamber are set forth in Brown, “The Physics of Continuous FlowCentrifugal Cell Separation,” Artificial Organs, 13(1):4-20 (1989), fromwhich FIG. 3A is taken.

As FIG. 3A shows, the surface hematocrit is least in the entry regionR_(e) of the chamber 10 near the WB inlet port 20. As FIG. 3 shows, thevelocity at which the RBC settle toward the high-G wall 18 in responseto centrifugal force is greatest in the entry region R_(e). Because thesurface hematocrit is the least, there is more plasma volume to displacein the entry region R_(e).

This, in turn, increases the radial velocity at which plasma isdisplaced by the separating RBC mass in response to the centrifugalforce field. As the RBC mass moves toward the high-G wall 18, the plasmais displaced in a radial flow path toward the low-G wall 16. As aresult, relatively large radial plasma velocities occur in the entryregion R_(e).

These large radial velocities toward the low-G wall 16 elute largenumbers of platelets from the RBC mass. As a result, fewer plateletsremain entrapped on the interface 26 here than elsewhere in the chamber10.

The purposeful arrangement of the ports 20; 22; and 24 in the separationchamber 10 also contributes to further enhanced elution of platelets.The WB inlet port 20 is diametrically spaced from the RBC collectionport 22, but the WB inlet port 20 is alongside the PRP collection port24. This isolation between the WB inlet port 20 and the RBC collectionport 22 forces the RBC to traverse the entire axial length of thechamber 10 during processing. This maximizes its exposure to thecentrifugal force field.

The isolation between the RBC collection port 22 and the PRP collectionport 24 directs the RBC toward the RBC collection port 22. At the sametime, it directs the PRP stream in the opposite direction toward the PRPcollection port 24.

Furthermore, due to the displaced low-G wall 16, the distance betweenthe low-G wall 16 and the interface 26 increases between the region ofthe RBC collection port 22 and the PRP collection port 24. As a result,the plasma layer along the interface 26 increases in radial depth in theintended direction of PRP flow, i.e., away from the RBC collection port22 and toward the axially spaced PRP collection port 24. The plasma nearthe RBC collection port 22 is closer to the high-G centrifugation fieldthan the plasma near the PRP collection port 24.

This shift in the relative position of the plasma between the two ports22 and 24 causes the lighter plasma to move along the interface 26. Theplasma moves swiftly away from the relatively more confined regioncloser to the high-G field (i.e., next to the RBC collection port 22),toward the relatively more open region closer to the low-G field (i.e.,next to the PRP collection port 24).

This swiftly moving axial plasma flow actually drags the interface26—and platelets entrapped within in—continuously toward the PRPcollection port 24. There, the radial plasma velocities are the greatestto supply the greatest elution effect, lifting the entrapped plateletsfree of the interface 26 and into the PRP stream for collection throughthe port 24.

The close juxtaposition of the WB inlet port 20 and the PRP collectionport 24 will alone result in improved platelet elutriation in thechamber 10, without altering the radial position of the low-G wall 16relative to the interface 26. The enhanced radial flow conditions willalone keep the majority of the platelet population in suspensions in thePRP for collection.

The remaining minority of the platelet population constitutes plateletsthat are physically larger. These larger platelets typically occupy over15×10⁻¹⁵ liter per platelet (femtoliters, or cubic microns), and someare larger than 30 femtoliters. In comparison, most platelets averageabout 8 to 10 femtoliters (the smallest of red blood cells begin atabout 30 femtoliters).

These larger platelets settle upon the interface 26 quicker than mostplatelets. These larger platelets are most likely to become entrapped inthe interface 26 near the RBC collection port 22.

The axial plasma flow conditions established along the interface 26 bythe displaced low-G wall 16 moves these larger, faster settlingplatelets with the interface 26. The axial plasma flow moves the largerplatelets toward the PRP collection port 24 into the region of highradial plasma flow. The high radial plasma flow lifts the largerplatelets from the interface 26 for collection.

The complementary flow conditions continuously lift platelets of allsizes from the interface 26 next to the PRP collection port 24. Theywork to free platelets of all sizes from the interface 26 and to keepthe freed platelets in suspension within the PRP.

Simultaneously (as FIG. 3 shows), the counterflow patterns serve tocirculate the other heavier components of the interface 26 (thelymphocytes, monocytes, and granulocytes) back into the RBC mass, awayfrom the PRP stream.

As a result, the PRP exiting the PRP collection port 24 carries a highconcentration of platelets and is substantially free of the other bloodcomponents.

B. Two Stare Separation Systems

FIGS. 6 to 10 show the physical construction of a two stage axial flowsystem 27 that embodies the features and benefits already discussed, aswell as additional features and benefits.

As FIG. 6A shows, the system 27 includes an assembly 28 of twodisposable separation and collection containers 31A and 31B linked bytubing to an umbilicus 29. The separation containers 31A/31B andassociated tubing can be made of low cost medical grade plasticmaterials, like plasticized PVC.

In use, the container 31A constitutes an axial flow chamber in which RBCand PRP are separated from whole blood in a first processing stage. Thecontainer 31A embodies the features of the axial flow chamber 10, aspreviously described.

In use, the container 31B constitutes an axial flow chamber in which thePRP is further separated into platelet concentrate and platelet-depletedplasma (also called platelet-poor plasma) in a second processing stage.The specification and drawings will refer to platelet concentrate as PCand platelet-poor plasma as PPP. The container 31B embodies otheraspects of the invention, which will be described in greater detaillater.

In this configuration, the assembly 28 can be used in association with acommercially available blood processing centrifuge, like the CS-3000®Blood Separation Centrifuge made and sold by the Fenwal Division ofBaxter Healthcare Corporation (a wholly owned subsidiary of the assigneeof the present invention).

As FIG. 7A best shows, the commercially available centrifuge includes arotor 30 that carries two holders 32A and 32B, one for each container31A and 31B. FIG. 6A shows the holder 32A for the first container 31A.FIG. 6B shows the holder 32B for the second container 31B.

As FIGS. 6A/B show, each holder 32A/32B can be pivoted opened to receiveits separation container 31A/31B. Each holder 32A/32B can then bepivoted closed (as FIG. 8 shows) to capture and enclose the associatedseparation container 31A/31B during processing.

In conventional use, the rotor 30 rotates (typically at about 1600 RPM),subjecting the holders 32A/32B and their entrapped separation containers31A/31B to a centrifugal force field. Typically, the centrifugal forceis field is about 375 G's along the high-g wall of the assembly 28.

As FIG. 6A shows, the first stage container 31A includes a series ofports through which the tubing umbilicus 29 conveys fluid. The container31A receives WB through the port 34 for centrifugal separation into RBCand PRP. The ports 36 and 38 convey separated RBC and PRP, respectively,from the first container 31A.

PRP is conveyed from the first container 31A into the second stagecontainer 31B. The second container 31B receives PRP through the port 35for centrifugal separation into PC and PPP. The port 37 conveys PPP fromthe container 31B, leaving the PC behind within the container 31B forcollection. A normally closed outlet port 39 is provided to later conveythe PC from the container 31B.

As FIG. 7B best shows, the umbilicus 29 connects the rotating separationcontainers 31A/31B with pumps and other stationary components locatedoutside the rotor 30. The stationary components include a pump P1 forconveying WB into the first container 31A. A pump P2 conveys PRP fromthe first container 31A to the second container 31B. An interfacedetector 33 senses the boundary between the RBC and plasma to controlthe operation of the pump P2.

The pump P2 pulls PRP away from the container 31A, until the detector 33senses the presence of RBC. This indicates that the boundary between theRBC and the plasma has “spilled” past the detector 33. The pump P2 thenpumps back toward the first container 31A until the sensed “spill-over”clears the interface detector 33. The pump P2 then reverses again topull PRP away from the container 31A until the detector 33 sensesanother “spill-over.” This process repeats itself.

Employing the well-known Cullis seal-less centrifuge principle, anon-rotating (zero omega) holder (not shown) holds the upper portion ofthe umbilicus 29 in a non-rotating position above the rotor. The holder40 (see FIG. 7A) rotates the mid-portion of the umbilicus 29 at a first(one omega) speed about the rotor 30. The holder 42 (also see FIG. 7A)rotates the lower end of the umbilicus 29 at a second speed twice theone omega speed (the two omega speed). The rotor 30 also rotates at thetwo omega speed.

This relative rotation of the umbilicus 29 and the rotor 30 keeps theumbilicus 29 untwisted, in this way avoiding the need for rotatingseals.

Each separation container 31A and 31B conforms to the interiorconfiguration defined by its respective holder 32A and 32B, when closed.

1. First Stage Separation Chamber

More particularly, as FIG. 6A shows, the holder 32A for the first stagecontainer 31A includes a preformed high-G surface 44, also shown in FIG.9A. The holder 32A also includes a facing preformed low-G surface 46,also shown in FIG. 9B. As FIG. 6A shows, the surface 46 is formed on apressure plate 47 that is inserted into the holder 32A.

When closed, the holder 32A sandwiches the flexible separation container31A between the high-G surface 44 and the surface of the low-G surface46 (as FIG. 8 shows).

As FIGS. 6A and 9A show, the high-G surface 44 includes a prescribedrecessed region 48 from which a pattern of raised sealing surfaces 50project. When the holder 32A is closed, the pressure plate 47 pressesthe low-G surface 46 against the sealing surfaces 50. The pressure platesurface 46 crimps the walls of the separation container 31A closed alongthese sealing surfaces 50. This forms a prescribed peripherally sealedregion within the container 31A occupying the recessed region 48.

When filled with blood during processing, the peripherally sealed regionof the container 31A expands against the high-g surface 44 and thefacing low-g surface of the pressure plate 46, assuming their prescribedcontours.

As FIGS. 6A and 9A best show, the pattern of the raised sealing surfaces50 establishes first, second, and third port regions 52; 54; and 56extending into the recessed region 48. The first port region 52 receivesthe WB inlet port 34 of the container 31A. The second port region 54receives the RBC collection port 36 of the container 31A. The third portregion 56 receives the PRP collection port 38 of the container 31A.

As FIGS. 6A and 9A show, the first port region 34 (receiving WB inletport 34) and the third port region 56 (receiving the PRP collection port38) enter the recessed region 48 on the same transverse edge of thehigh-G surface 44 (which is shown as the top edge in the drawings). Thesecond port region 54 (receiving the RBC collection port 36) enters therecessed region 48 through a passage 49 that opens on the oppositetransverse edge of the high-G surface 44 (which is shown as the bottomedge in the drawings). Of course, as previously stated, the relativeorientation of the transverse top and bottom edges could be reversed.

When the holder 32A is closed, mating regions 52A; 54A; and 56A on thelow-G pressure plate 46 (see FIG. 9B) register with the first, second,and third port regions 52; 54; and 56 on the high-G surface 44 toreceive the WB, RBC and PRP ports 34; 36; and 38 (see FIG. 8 also).

In the illustrated embodiment, the low-G pressure plate surface 46preferably tapers outward toward the high-G surface at a slope of about0.25 degree.

When closed, the holder 32A thereby shapes the peripherally sealedregion of the container 31A to establish an axial flow processingchamber 10 like that shown in FIGS. 1 to 3.

In use, the first stage separation chamber 32B preferably presents aneffective collection area of between about 70 to about 120 cm², with anassociated processing volume of between about 45 ml to about 100 ml.

2. The Second Stage Separation Chamber

As FIG. 6B shows, the holder 32B for the second stage container 31B,like the other holder 32 includes a preformed high-G surface 51, whichFIG. 10A also shows. The holder 32B also includes a facing preformedlow-G pressure surface 53 formed on an insertable pressure plate 55.

Like the holder 32A, the high-G surface 51 of the holder 32B includes arecessed region 57 from which a pattern of raised sealing surfaces 59project (see FIGS. 6B and 10A).

Like the holder 32A, when the holder 32B is closed, the pressure platelow-G surface 53 presses against the sealing surfaces 59. This crimpsthe walls of the separation container 31B closed along the sealingsurfaces 59. The interior configuration of the second stage axial flowseparation chamber 61 is thereby formed, as FIG. 10B shows.

As FIG. 10B shows, the pattern of the raised sealing surfaces 59establishes first and second regions R1 and R2 within the chamber 61.The first region R1 communicates with the PRP inlet port 35 of thecontainer 31B. The second port region R2 communicates with the PPPcollection port 37 of the container 31B.

The raised sealing surfaces 59 also establish an interior wall 63 thatseparates the first and second regions R1 and R2. The wall 63 stretchesinto the chamber 61, extending in the same direction as the axial flowpath. The wall 63 terminates within the chamber 61 to form a passage 65linking the two regions R1 and R2. It should be appreciated thatposition of the wall 63 within the chamber 61 can vary. It can be closerto the PRP inlet port 35 than shown in FIG. 10B, thereby decreasing thesize of the first region R1, and vice versa.

As just described, the configuration of the second stage chamber 61 islike that shown in FIGS. 11 to 13 in Cullis et al. U.S. Pat. No.4,146,172. The Cullis et al. '172 Patent is incorporated into thisSpecification by reference.

A chamber like that shown in FIGS. 11 to 13 of the Cullis et al. '172Patent has been in widespread commercial use in association with theCS-3000® Blood Separation Centrifuge for use in separating PC and PPPfrom PRP. The commercial chamber bears the trade designation “A-35Chamber.”

The prior A-35 Chamber typically has a collection area of about 160 cm²for separating PRP into PC and PPP. When used for this purpose, thischamber typically presents a radial thickness (or depth) on the order ofabout 1.4 cm. The chamber thereby has a processing volume of about 200mL.

Conventional wisdom believed that the processing volume for second stageplatelet separation chamber should exceed the processing volume of thefirst stage separation chamber.

The larger processing volume was believed to be beneficial, because itgave the platelets more time to separate (or “sediment”) from the PRPwithin the chamber. Conventional wisdom also believed that the largerdesired processing volume in the second stage chamber would subject theplatelets to less damage or activation due to shear stress duringprocessing (see, e.g., column 10, lines 26 to 39 of the Cullis et al.'172 Patent).

According to the present invention, the axial flow processing chamber 61shown in FIG. 10B has a significantly smaller processing volume,compared to the prior A-35 Chamber.

In one operative embodiment, the chamber 61 configured according to theinvention presents the same collection area as the prior A-35 Chamber(i.e., about 160 cm²), but has a maximum radial (or channel) depth ofonly 2 mm. In this operative embodiment, the chamber 61 presents aprocessing volume of just 30 mL, compared to the 200 mL processingvolume typical for the prior A-35 Chamber.

Surprisingly, despite its considerably smaller processing volume andradial depth, the following Example demonstrates that the chamber 61provides a significant increase in platelet collection efficiencies,compared to the prior A-35 Chamber.

EXAMPLE 1

A study compared the conventional 200 ml A-35 chamber to the 30 ml,reduced depth chamber described above (which will be called the “30 mlChamber”). Both chambers had a collection area of 160 cm².

The study used a paired run protocol. During the protocol, 59 normaldonors underwent a platelet collection procedure with the A-35 chamber.The same donors underwent another platelet collection procedure with the30 ml Chamber. The order of the collection procedures was randomizedamong the donors, with the procedures performed about a month apart.

Both procedures were conducted on a CS-3000® Centrifuge operated at aspeed of 1600 RPM. All operating parameters for the first procedure wererepeated in the second procedure. Six different blood centersparticipated in the study.

The results were correlated and statistically verified.

The study showed that the 30 ml Chamber provided significantly improvedplatelet collection. Compared to the A-35 Chamber, the 30 ml Chambershowed a 13.3% increase in platelet yield (p<0.0001), which represents asignificant increase in the net number of platelets collected during agiven procedure.

Compared to the A-35 Chamber, the 30 ml Chamber provided increasedplatelet yields without damage or activation of the platelets. Theplatelet concentrate collected using the 30 ml Chamber could be filteredimmediately after resuspension, without platelet loss. On the otherhand, platelet concentrate collected using the A-35 Chamber required arest period of at least 2 hours before it could be filtered withoutincurring a significant loss in platelet count.

Using the conventional dimensionless Reynolds Number (Re) as a point ofcomparison, one would conclude that the nature of the fluid flow in theA-35 Chamber and the 30 ml Chamber are virtually identical. The A-35 hasa Re of 2.9, and the 30 ml Chamber has a Re of 7, which are notsignificantly different values.

One aspect of the invention provides a new dimensionless parameter (λ)that more accurately characterizes the combined attributes of angularvelocity, channel thickness, kinematic viscosity, and axial height ofthe platelet separation chamber 61. The new parameter (λ) is expressedas follows:$\lambda = \frac{\left( {2\quad \Omega \quad h^{3}} \right)}{\left( {\upsilon \quad Z} \right)}$

where:

Ω is the angular velocity (in rad/sec);

h is the radial depth (or thickness) of the chamber (in cm);

υ is the kinematic viscosity of the fluid being separated (in cm²/sec);and

Z is the axial height of the chamber (in cm).

As Table 1 shows, the parameter (λ) value clearly characterizes anddifferentiates the unique nature and domain of the flow regimeestablished within the chamber 61 (referred to as the “New” chamber),compared to the conventional A-35 chamber.

TABLE 1 Chamber Type A-35 Chamber New Fluid Plasma Plasma Volume mL 20030 υ cm²/sec 0.012 0.012 Flow Rate mL/min 25 25 Speed RPM 1600 1600Thickness cm 1.4 0.2 Height cm 15 15 λ 2Ωh³/υZ 5109 14 Re Q/υZ 3.5 7

As Table 1 shows, the parameter (λ) value for the prior A-35 Chamber is5109. The parameter (λ) value for the chamber that embodies the featuresof the invention is only 14, less than 1% of the prior chamber.

According to this aspect of the invention, a parameter (λ) value for achamber that is less than about 700 will produce significantly greaterplatelet yields. As the parameter (λ) value of a given chamberincreasingly exceeds about 700, the chamber produces flow conditionsthat lead to greater overall shear stress during processing (leading toplatelet activation) and to greater Coriolis-effect swirling (whichlimits the effective surface area available for platelet perfusion).

The new parameter (λ) value expresses for a given rotating frame ofreference what the magnitude of Coriolis-effect swirling and shearstress will be. The parameter (λ) value has the same meaning whether theflow within the chamber is axial (i.e., along the axis of rotation) orcircumferential (i.e., about the axis of rotation). Regardless of thedirection of flow with respect to the rotational axis, the lower theabsolute parameter (λ) value is for a given system, the lower will bethe expected magnitude of Coriolis-effect swirling in the system. Thechamber 61 has a parameter (λ) value that is less than about 700, it isbetter perfused during processing and subjects the platelets to lessshear stress, even at dramatically reduced chamber depths (i.e. radialthickness).

II. Enhanced Yield Circumferential Flow Chambers

The aspects of the invention previously described in the context of anaxial flow blood separation chamber can also be employed in providing acircumferential flow blood processing chamber with enhanced plateletseparation efficiencies.

FIGS. 11 to 13 show, in diagrammatic fashion, a circumferential flowcentrifugal blood processing chamber 58 that embodies the features ofthe invention.

In use, the chamber 58 rotates on a rotor 60 about an axis 62 (see FIG.12), to thereby create a centrifugal field within the chamber 58. Justas with the axial flow chamber 10 shown in FIGS. 1 to 3, the centrifugalfield extends radially from the axis through the chamber 58. As FIG. 13shows, the chamber wall 64 closest to the axis constitutes the low-Gwall, and the chamber wall 66 farthest from the axis constitutes thehigh-G wall.

While rotating, the chamber 58 receives WB through a first port 68. TheWB follows a circumferential flow path in the chamber 58; that is, itflows in a circumferential path about the rotational axis 62 (as FIG. 12best shows). For this reason, the chamber 58 is called a circumferentialflow blood processing chamber.

In this geometry, the transverse top and bottom edges of the chamber 58(which lie along the circumferential flow path) are usually longer thanthe longitudinal side edges (which lie across the circumferential flowpath). The circumferential flow chamber 58 usually forms the shape of atube that is elongated in the direction of rotation. Still, otherconfigurations defining a circumferential flow path can be used.

WB separates within the tubular chamber 58 under the influence of thecentrifugal field into RBC and PRP. As FIG. 13 shows, the higher densityRBC move toward the high-G wall 66, displacing the lighter density PRPtoward the low-G wall 64. The interface 26 (previously described) formsbetween them. A second port 70 draws the RBC from the chamber 58 forcollection. A third port 72 draws the PRP from the chamber 58 forcollection.

According to the invention, the PRP collection port 72 and the WB inletport 68 are juxtaposed so that the PRP exits the circumferential flowchamber 58 in the same region where WB enters the chamber 58. In theillustrated embodiment, as shown in FIG. 11, the PRP collection port 72is located along the same longitudinal side edge of the circumferentialflow chamber 58 as the WB inlet port 68.

Also according to the invention, the RBC collection port 70 and the PRPcollection port 72 are arranged so that PRP exits the chamber 58 in aregion opposite to the region where RBC exit the chamber 58, relative tothe circumferential flow of WB in the chamber 58. In the illustratedembodiment, as FIG. 11 shows, the RBC collection port 70 is located onthe longitudinal side edge that is opposite to longitudinal side edgewhere the WB inlet and PRP collection ports are located.

The chamber 58 shown in FIGS. 11 to 13 differs significantly from priorcircumferential flow blood separation chambers 58A and 58B, which areshown in FIGS. 14 and 15. The prior circumferential flow chambers 58A/Bpurposely located the PRP collection port 72 away from the WB inlet port68.

In the prior circumferential flow chamber 58A shown in FIG. 14, the PRPcollection port 72 occupies one side edge, diametrically opposite to theRBC collection port 70, which occupies the other side edge. In thisconstruction, the WB inlet port 68 is located in a side wall of thechamber 58A between the two side edges.

In the prior circumferential flow chamber 58B shown in FIG. 15, the PRPcollection port 72 occupies one side edge, while the WB inlet port 68and the RBC outlet port occupies the opposite side edge, oppositelyspaced away from the PRP collection port 72 relative to thecircumferential flow of WB in the chamber 58B.

In both the FIG. 14 construction and the FIG. 15 construction, no portsare located on the top and bottom transverse edges of the chamber 58B.Neither chamber 58A and 58B has a port with an axis that extendsparallel to the axis of rotation.

FIG. 13 diagrammatically shows the enhanced platelet separation effectdue to the adjacent positions of the WB inlet port 68 and the PRPcollection port 72 in the circumferential flow chamber 58 that embodiesthe invention. The effect is generally the same as that shown in FIG. 3,except the chamber 58 is oriented differently to establish thecircumferential flow pattern.

As FIG. 13 shows, the PRP collection port 72 draws PRP from the chamber58 where velocity at which the RBC settle toward the high-G wall 66 inresponse to centrifugal force is the greatest, i.e., next to the WBinlet port 68. Here, too, is where the radial plasma velocity is thegreatest to lift platelets from the interface 26, and to keep them insuspension within the plasma for transport out the PRP collection port72.

The WB inlet port 68 is oppositely spaced from the RBC collection port70 (in the circumferential flow direction), forcing the RBC to traversethe entire axial length of the chamber 58, thereby maximizing theirexposure to the centrifugal separation forces. The isolation between theRBC collection port 70 and the PRP collection port 72 also directs theRBC toward the RBC collection port 70, while directing the PRP stream inthe opposite direction toward the PRP collection port 72.

Like the chamber 10 shown in FIG. 3, the low-G wall 64 is preferablydisplaced inward toward the interface 26 near the RBC collection port70. As a result, the radial distance between the low-G wall 64 andinterface 26 is greater near the PRP collection port 72 than near theRBC collection port 70.

As previously described with reference to FIG. 3, the displaced low-Gwall 64 causes the lighter plasma to move along the interface 26 swiftlyaway from the relatively more confined region next to the RBC collectionport 70, toward the relatively more open region next to the PRPcollection port 72. The same beneficial effect results: thecircumferential plasma flow drags the interface 26—and larger, fastersettling platelets entrapped within in—continuously toward the PRPcollection port 72, where the radial plasma velocities are the greatestto supply the greatest elution effect. The counterflow patterns alsoserve to circulate the other heavier components of the interface(lymphocytes, monocytes, and granulocytes) back into the RBC mass, awayfrom the PRP stream.

As FIG. 13 shows, the low-G wall 64 continuously tapers in the directionof the circumferential flow path, e.g., away from the PRP collectionport 72 and in the direction of axial flow path of the WB. The sameresult can be obtained without continuously or uniformly tapering thelow-G wall 16 along the entire length of the axial flow path between thePRP collection port 72 and the RBC collection port 70. The low-G wall 16can begin its taper farther away from the PRP collection port 24 thanFIG. 13 shows, closer to the region of the RBC collection port 70.

The circumferential flow chamber 58 that embodies the invention can bevariously constructed. FIGS. 16 and 17 show the physical construction ofone preferred circumferential flow chamber assembly 74 that embodies thefeatures of the invention. FIGS. 25 and 26 show the physicalconstruction of an alternative circumferential flow assembly 76.

Either assembly 74 or 76 can be used in association with a bloodprocessing centrifuge 78, like that shown in FIGS. 18 and 19. Furtherdetails of this centrifuge construction are set forth in copending U.S.patent application Ser. No. 07/814,403, filed Dec. 23, 1991 and entitled“Centrifuge with Separable Bowl and Spool Elements Providing Access tothe Separation Chamber”.

As FIG. 20 shows, the centrifuge 78 includes a bowl element 80 and aspool element 82. The bowl and spool elements 80 and 82 can be pivotedon a yoke 85 between an upright position, as FIG. 20 shows, and asuspended position, as FIG. 21 shows.

When upright, the bowl and spool elements 80 and 82 are presented foraccess by the user. A mechanism permits the spool and bowl elements 80and 82 to assume a mutually separated position, as FIG. 20 shows. Inthis position, the spool element 80 is at least partially out of theinterior area of the bowl element 82 to expose the exterior spoolsurface for access. As FIG. 22 shows, when exposed, the user can wrapeither circumferential flow chamber assembly 74 or 76 about the spoolelement 82.

The mechanism also permits the spool and bowl elements 80 and 82 toassume a mutually cooperating position, as FIG. 23 shows. In thisposition, the spool element 82 and the chosen circumferential flowchamber assembly 74 or 76 are enclosed within the interior area of thebowl element 80, as FIG. 23 shows. A processing chamber 83 is formedbetween the interior of the bowl element 80 and the exterior of thespool element 82. The chosen circumferential flow chamber assembly 74 or76 is carried with and assumes the contours of the processing chamber83.

When closed, the spool and bowl elements 80 and 82 can be pivoted as anassembly into a suspended position, as FIG. 21 shows. When suspended,the bowl and spool elements 80 and 82 are in position for operation. Inoperation, the centrifuge 78 rotates the suspended bowl and spoolelements 80 and 82 about an axis.

In the illustrated embodiments, each circumferential flow chamberassembly 74 and 76 provides multi-stage processing. A first stageseparates RBC and PRP from WB. A second stage separates PC and PPP fromthe PRP.

While the interior of either circumferential flow chamber assembly 74 or76 can be variously arranged, FIGS. 16/17 and 18/19 show the interior ofthe alternative circumferential flow chambers divided into twoside-by-side processing compartments 84 and 86. In use, centrifugalforces in the first compartment 84 separate whole blood into RBC andPRP. Centrifugal forces in the second processing compartment 86 separatethe PRP from the first stage into PC and PPP.

In both alternative circumferential flow chambers, a first peripheralseal 88 forms the outer edge of the circumferential flow chamberassembly 74 or 76. A second interior seal 90 divides the circumferentialflow chamber assembly 74 or 76 into the first processing compartment 84and the second processing compartment 86. The second seal 90 extendsgenerally parallel to the rotational axis of the chamber assembly 74 or76; that is, it extends across the circumferential flow of the chamberassembly 74 or 76. The second seal 90 constitutes a longitudinal edgecommon to both first and second processing compartments 84 and 86.

Each processing compartment 84 and 86 serves as a separate and distinctseparation chamber and will therefore be referred to as such.

In each alternative circumferential flow chambers, five ports92/94/96/98/100 open into the compartmentalized areas formed in theprocessing chamber assembly 74 or 76. The ports 92/94/96/98/100 arearranged side-by-side along the top transverse edge of the respectivechamber 84 and 86.

The ports 92/94/96/98/100 are all axially oriented; that is, their axesare aligned with the axis of rotation, transverse the circumferentialfluid flow path within the chamber assembly 74 or 76 itself. Three ports92/94/96 serve the first chamber 84. Two ports 98/100 serve the secondchamber 86.

In both alternative circumferential flow chamber assemblies 74 and 76,an umbilicus 102 (see FIG. 24) attached to the ports 92/94/96/98/100interconnects the first and second chambers 84 and 86 with each otherand with pumps and other stationary components located outside therotating components of the centrifuge 78.

As FIG. 21 shows, a non-rotating (zero omega) holder 104 holds the upperportion of the umbilicus 102 in a non-rotating position above thesuspended spool and bowl elements 80 and 82. A holder 106 on the yoke 85rotates the mid-portion of the umbilicus 102 at a first (one omega)speed about the suspended spool and bowl elements 80 and 82. Anotherholder 108 (see FIG. 22) rotates the lower end of the umbilicus 102 at asecond speed twice the one omega speed (the two omega speed), at whichthe suspended spool and bowl elements 80 and 82 also rotate. As beforestated, this known relative rotation of the umbilicus keeps ituntwisted, in this way avoiding the need for rotating seals.

Using either alternative circumferential flow chamber assembly 74 or 76,the two omega speed at which the suspended spool and bowl elements 80and 82 rotate is about 3400 RPM. Given the dimensions of the spool andbowl elements 80 and 82, 3400 RPM will develop a centrifugal force fieldof about 900 G's along the high-G wall 66 of the chambers 84 and 86.

A. The First Stage Processing Chamber

In the embodiment shown in FIGS. 16 and 17, the first port 92 comprisesthe previously described PRP collection port (identified by referencenumeral 72, as in FIGS. 11 to 13). The second port 94 comprises thepreviously described WB inlet port (identified by reference numeral 68,as in FIGS. 11 to 13). The third port 96 comprises the previouslydescribed RBC collection port (identified by reference numeral 70, as inFIGS. 11 to 13).

A third interior seal 110 is located between the PRP collection port 72and the WB inlet port 68. The third seal 110 includes a first region 112that is generally parallel to the second interior seal 90, therebyextending across the circumferential WB flow path. The third interiorseal 110 then bends in a dog-leg portion 114 away from the WB inlet port68 in the direction of circumferential WB flow. The dog-leg portion 114terminates beneath the inlet of the PRP collection port 72.

A fourth interior seal 116 is located between the WB inlet port 68 andthe RBC collection port 70. The fourth seal 116 includes a first region118 that is generally parallel to the second and third interior seals 90and 110, thereby extending across the circumferential WB flow path. Thefourth interior seal 116 then bends in a dog-leg portion 120 away fromthe RBC collection port 70 in the direction of circumferential WB flow.The dog-leg portion 120 extends beneath and beyond the dog-leg portion114 of the third seal 110. It terminates near the longitudinal side edgeof the first chamber 84 that is opposite to the longitudinal side edgeformed by the second interior seal 90.

Together, the third and fourth interior seals. 110/116 form a WB inletpassage 122 that first extends along the axis of rotation (i.e., betweenthe first regions 112/118 of the two seals 110/116). The WB inletpassage 122 then bends to open in the direction of intendedcircumferential flow within the first chamber 84 (i.e., between thedog-leg portions 114/120 of the two seals 110/116).

The WB inlet passage 122 first channels WB away from the WB inlet port68 in an axial flow path. It then channels WB circumferentially,directly into the circumferential flow path, where separation into RBCand PRP begins.

The third interior seal 110 also forms a PRP collection region 124within the first chamber 84 (i.e., between the third seal 110 and theadjacent upper portion of the first peripheral seal 88).

Together, the fourth interior seal 116, the second interior seal 90, andthe lower regions of the first peripheral seal 88 form a RBC collectionpassage 126 that extends first along the axis of rotation (i.e., betweenthe second interior seal 90 and the fourth interior seal 116). The RBCcollection passage 126 then bends in a circumferential path to open nearthe end of the intended WB circumferential flow path (i.e., between thedog-leg portion 120 of the fourth seal 116 and the lower region of theperipheral seal 88).

In the embodiment shown in FIGS. 18 and 19, the first port 92 comprisesthe RBC collection port (identified by reference numeral 70, as in FIGS.11 to 13). The second port 94 comprises the PRP collection port(identified by reference numeral 72, as in FIGS. 11 to 13). The thirdport 96 comprises the WB inlet port (identified by reference numeral 68,as in FIGS. 11 to 13).

As FIG. 18 shows, a third interior seal 110 is located between the PRPcollection port 72 and the WB inlet port 68. The seal 110 includes afirst region 112 that is generally parallel to the second interior seal90. It then bends in a dog-leg portion 114 away from the WB inlet port68 in the direction of circumferential WB flow. The dog-leg portion 114terminates beneath the inlet of the PRP collection port 72.

Together, the second and third interior seals 90 and 110 form a WB inletpassage 122, like the WB inlet passage 122 associated with the chamber84 shown in FIG. 16, except in a different location within the chamber.

As FIG. 18 shows, a fourth interior seal 116 is located between the PRPcollection port 72 and the RBC collection port 70. The fourth seal 116includes a first region 118 that is generally parallel to the second andthird interior seals 90 and 110, thereby extending across thecircumferential flow path. The fourth interior seal 116 then bends in adog-leg portion 120 away from the PRP collection port 72 in thedirection of circumferential WB flow. It terminates near thelongitudinal side edge of the first chamber 84 that is opposite to thelongitudinal side edge formed by the second interior seal 90.

Together, the fourth interior seal 116 and the upper regions of thefirst peripheral seal 88 form a RBC collection passage 126, like the RBCcollection passage 126 shown in FIG. 16, except that it is located atthe top of the chamber 84, instead of at the bottom.

As FIG. 18 shows, the third and fourth interior seals 110 and 116together also form a PRP collection region 124 within the first chamber,like the PRP collection region 124 shown in FIG. 16.

The dynamic flow conditions within each alternative circumferential flowchamber assembly 74 or 76 are the same. These conditions direct PRPtoward the PRP collection region 124 for collection through the inlet ofthe PRP collection port 72.

As FIGS. 16 and 18 show, the WB inlet passage 122 channels WB directlyinto the circumferential flow path immediately next to the PRPcollection region 124. Here, the radial flow rates of plasma aregreatest to lift platelets free of the interface and into the PRPcollection region 124.

The RBC collection passage 126 receives RBC at its open end and fromthere channels the RBC to the RBC collection port 70. As FIGS. 16 and 18show, the WB inlet passage 122 channels WB directly into the flow pathat one end of the first chamber 84, and the RBC collection passage 126channels RBC out at the opposite end of the flow path.

In each alternative circumferential flow chamber assembly 74 and 76 (asFIGS. 17 and 19 respectively show), the low-G wall 64 of the firstchamber 84 is offset toward the high-G wall 66 near the RBC collectionregion.

In the particular embodiments shown, the low-G wall 64 tapers into thechamber 84 in the direction of circumferential WB flow. The taperproceeds from the second interior seal 90 toward the oppositelongitudinal end of the chamber. FIG. 13 shows the tapering low-G wall64 from another perspective.

The tapering low-G wall 64 includes a stepped-up barrier 128 or dam inthe region where the RBC collection passage 126 opens. As FIGS. 16 and18 show for their respective chamber assembly, the stepped-up barrier128 extends from the low-G wall 64 across the entire chamber 84.

As FIG. 13 best shows from another perspective, the stepped-up barrier128 extends into the RBC mass and creates a restricted passage 129between it and the facing high-G wall 66. The restricted passage 129allows RBC present along the high-G wall 66 to move beyond the barrier128 for collection by the RBC collection passage 126. Simultaneously,the stepped-up barrier 128 blocks the passage of the PRP beyond it,keeping the PRP within the dynamic flow conditions leading to the PRPcollection region 124.

While various configurations can be used, in a preferred arrangement,the low-G wall 64 tapers about 2 mm into the chamber 74 where it joinsthe barrier 128. The barrier 128 extends from there at about a 45 degreeangle toward the high-G wall 66, forming a raised planar surface. Thepassage 129 formed between the planar surface and the high-G wall 66 isabout 1 mm to 2 mm in radial depth and about 1 mm to 2 mm incircumferential length.

As previously described (and as FIG. 13 shows) the configuration of thelow-G wall 64 creates a swift counterflow of plasma from the RBCcollection region toward the PRP collection region 124.

The desired contours for the low-G wall 64 of the alternative chamberassemblies 74 and 76 can be preformed on the exterior surface of thespool element 82. In the illustrated embodiment, the interior surface ofthe bowl element 82 is isoradial with respect to the rotational axis.

Also in both alternative embodiments (as FIGS. 16 and 18 show), the dogleg portion 120 of the RBC collection passage 126 is tapered. Due to thetaper, the passage 126 presents a greater cross section where it opensinto the chamber 84 than it does where it joins the axial first region118 of the RBC collection passage 126. FIG. 13 shows this taper fromanother perspective. In the illustrated and preferred embodiment, thedog leg portion 120 tapers from a width of about ¼ inch to ⅛ inch.

The taper of the dog leg portion 120 is preferably gauged relative tothe taper of the low-G wall 64 to keep the cross sectional area of theRBC collection passage 126 substantially constant. This keeps fluidresistance within the passage 126 relatively constant, while maximizingthe available separation and collection areas outside the passage 126.The taper of the dog leg portion 120 also facilitates the removal of airfrom the passage 126 during priming.

As FIGS. 16 and 18 best show, a ramp 130 extends from the high-G wall 66across the PRP collection region 124 in each alternative chamberassembly 74 and 76. As FIG. 24 shows from another perspective, the ramp130 forms a tapered wedge that restricts the flow of fluid toward thePRP collection port 72. As FIG. 25 shows, the ramp 130 forms aconstricted passage 131 along the low-G wall 64, along which the PRPlayer extends.

In the illustrated embodiment (see FIG. 22), a hinged flap 132 extendsfrom and overhangs a portion of the spool element 82. The flap 132 ispreformed to present the desired contour of the ramp 130.

When flipped down (as FIG. 22 shows in solid lines), the flap 132 issandwiched between the chosen chamber assembly 74/76 and the surroundingbowl element 80. The flap 132 presses against the adjacent flexible wallof the chamber assembly 74/76, which conforms to its contour to form theramp 130 within the chamber 84.

As shown diagrammatically in FIGS. 25A to C, the ramp 130 diverts thefluid flow along the high-G wall 66. This flow diversion changes theorientation of the interface 26 between the RBC (shown shaded in FIGS.25A/B/C) and the PRP (shown clear in FIGS. 25A/B/C) within the PRPcollection region 124. The ramp 130 displays the interface 26 forviewing through a side wall of the chamber assembly 74/76 by anassociated interface controller 134 (that FIGS. 30 and 31 show).

As will be described in greater detail later, the interface controller234 monitors the location of the interface 26 on the ramp 130. As FIGS.25A/B/C show, the position of the interface 26 upon the ramp 130 can bealtered by controlling the relative flow rates of WB, the RBC, and thePRP through their respective ports 68/70/72. The controller 234 variesthe rate at which PRP is drawn from the chamber 84 to keep the interface26 at a prescribed location on the ramp 26 (which FIG. 25B shows), awayfrom the constricted passage 131 that leads to the PRP collection port72.

The ramp 130 and associated interface controller 234 keep RBC, whiteblood cells, and lymphocytes present in the interface 26 from enteringthe PRP collection port 72. The collected PRP is thereby essentiallyfree of the other cellular components present in the interface 26.

B. The Second Stage Processing Chamber

In the embodiment of the chamber assembly shown in FIGS. 16/17, thefourth port 98 constitutes a PPP collection port 136, and the fifth port100 constitutes a PRP inlet port 138. In the embodiment shown in FIGS.18/19, the opposite is true: the fourth port 98 constitutes the PPPinlet port 138, and the fifth port 100 constitutes the PPP collectionport 136.

In each chamber assembly 74/76, the umbilicus 102 connects the PRPcollection port 72 of the first chamber 84 with the PRP inlet port 138of the associated second chamber 86. The second chamber 86 therebyreceives PRP from the first chamber 84 for further separation into PPPand PC. The umbilicus 102 conveys separated PPP from the second chamber86 through the associated PPP collection port 136. In each assembly74/76, the PC remains behind in the second chamber 86 for laterresuspension and collection.

In the alternative embodiments shown in FIGS. 16/17 and 18/19, a fifthinterior seal 140 extends between the PRP inlet port 138 and the PPPcollection port 136. The fifth seal 140 includes a first region 142 thatis generally parallel to the second seal 90, thereby extending acrossthe circumferential flow path. The fifth interior seal 140 then bends ina dog-leg portion 144 away from the PRP inlet port 138 in the directionof circumferential PRP flow within the second chamber 86. The dog-legportion 144 terminates near the longitudinal side edge of the secondchamber 86 that is opposite to the longitudinal side edge formed by thesecond interior seal 90.

In the FIGS. 16/17 embodiment, the fifth interior seal 140, the secondinterior seal 90, and the lower regions of the first peripheral seal 88together form a PPP collection passage 146 that extends first along theaxis of rotation (i.e., between the second interior seal 90 and thefifth interior seal 140) and then bends in a circumferential path toopen near the end of the intended PRP circumferential flow path (i.e.,between the dog-leg portion 144 of the fifth seal 140 and the lowerregion of the peripheral seal 88). The PPP collection passage 146receives PPP at its open end and from there channels the PPP to the PPPcollection port 136.

In the FIGS. 18/19 embodiment, a similar PPP collection passage 146 isformed between the fifth interior seal 140 and the upper region of theperipheral seal 88.

In each alternative circumferential flow chamber assembly 74/76, PRPentering the second chamber 86 via the PRP inlet port 138 is caused toflow first in an axial path from the axially oriented PRP inlet port 138alongside the axially extending fifth seal 140. The flow direction ofthe PRP then turns to a circumferential path away from the fifth seal140 toward the opposite longitudinal side edge.

The centrifugal forces generated during rotation of the chamber separatethe PRP into PC and PPP. The more dense PC separate out into a layerthat extends along the high-G wall 66. The less dense PPP is displacedtoward the low-G wall 64 for collection through the PPP collectionpassage 146.

The inventor has discovered that the introduction of PRP along an axialflow path parallel to the axis of rotation into a circumferential flowpath about the axis of rotation creates a non-turbulent vortex region148, called a Taylor column, at the outlet of the PRP inlet port 138, asFIG. 26 shows.

The vortex region 148 circulates about an axis that is aligned with theaxis of the PRP inlet port 138. The vortex region 148 stretches from theoutlet of the port 138 longitudinally across the circumferential flowpath of the chamber 86. As FIG. 26 shows, the vortex region 148circulates the PRP about its axis and directs it into the desiredcircumferential flow path within the chamber 86.

Within the vortex region 148, axial flow velocity decreases in agenerally linear fashion across the circumferential flow path of thechamber 86. This occurs as the axial flow of fluid entering the chamber86 perfuses uniformly into a circumferential flow entering theseparation zone.

A similar vortex region 148 forms at the opposite longitudinal end ofthe second chamber 86 at the entrance to the PPP collection passage 146,as FIG. 26 also shows.

The vortex region 148 created at the outlet of the PRP inlet port 138uniformly disperses PRP in the desired circumferential flow path intothe centrifugal field. This maximizes the exposure of the entering PRPto the effects of the centrifugal field across the effective surfacearea of the second chamber 86. Maximum possible separation of PC fromthe entering PRP results.

It should be noted that similar vortex region 148 flow conditions areformed in the first chamber 84 as well, where fluid either enters orleaves the established circumferential flow path through an axial flowpath. As FIG. 26 shows, a vortex region 148 condition thereby forms atthe entrance of the WB inlet passage 122. Another vortex region 148condition forms at the opposite longitudinal end at the entrance of theRBC collection passage 126.

In both alternative chamber assemblies 74/76 (as FIGS. 17 and 19 show),the low-G wall 64 preferably tapers into the second chamber 86 in thedirection of circumferential PRP flow. The taper proceeds from thesecond interior seal 90 toward the opposite longitudinal end of thesecond chamber 86.

Also in both alternative chamber assemblies 74/76 (as FIGS. 16 and 18show), the circumferential leg of the associated PPP collection passage146 is tapered. Due to the taper, the leg presents a greater crosssection where it opens into the second chamber than it does where itjoins the axial portion of the PPP collection passage 146. In theillustrated and preferred embodiment, the leg tapers from a width ofabout ¼ inch to ⅛ inch.

As with the taper of the dog leg portion 120, the taper of thecircumferential leg of the PPP collection passage 146 is preferablygauged relative to the taper of the low-G wall 64 to keep the crosssectional area of the PPP collection passage 146 substantially constant.This keeps fluid resistance within the passage 146 relatively constant.The taper of the circumferential leg of PPP collection passage 146 alsofacilitates the removal of air from the passage 146 during priming.

The dimensions of the various regions created in the processing chambercan of course vary according to the processing objectives. Table 2 showsthe various dimensions of a representative embodiment of a processingchamber of the type shown in FIGS. 16/17 or 18/19. Dimensions A throughF referenced in Table 2 are identified for their respective chamberassemblies in FIGS. 16 and 18.

TABLE 2 Overall length (A): 19½ inches Overall height (B): 2{fraction(13/16)} inches First Stage Processing Chamber Length (C): 10⅛ inchesWidth (D): 2⅜ inches Maximum Radial Depth in Use: 4 mm Second StageProcessing Chamber Length (E): 8{fraction (13/16)} inches Width (F): 2⅜inches Maximum Radial Depth in Use: 4 mm Port Spacing (center line tocenter line): ⅜ inch

III. Systems Using the Enhanced Yield Circumferential Flow Chamber forPlatelet Separation and Collection

The two stage circumferential flow chambers shown in either FIGS. 16/17or FIGS. 18/19 can be used to do continuous platelet collection. Thechambers can be used in associated either with a system 150 that employsone phlebotomy needle (as FIG. 27 shows) or with a system 152 thatemploys two phlebotomy needles (as FIG. 28 shows). In each system 150and 152, an associated processing controller 154 automates thecollection procedure to the fullest extent possible.

A. Single Needle Enhanced Yield Platelet Collection System

The platelet collection system 150 shown in FIG. 27 employs one, singlelumen phlebotomy needle 156. FIG. 21 generally depicts this singleneedle system 150 when mounted for use on the centrifuge 78.

The processing controller 154 operates the single needle system 150 in adraw cycle and a return cycle.

During the draw cycle, the controller 154 supplies the donor's WBthrough the needle 156 to a chosen one of the processing chamberassemblies 74/76. There, the WB is centrifugally separated into RBC, PC,and PPP.

During the return cycle, the controller 154 returns RBC and PPP to thedonor through the needle 156, while separation within the chosenprocessing chamber assembly 74/76 continues without interruption. Theharvested PC is retained for long term storage. If desired, all or somePPP can be retained for storage, too.

The system 150 includes a draw reservoir 158, which pools a quantity ofthe donor's WB during the draw cycle. The system 150 also includes areturn reservoir 160, where a quantity of RBC collect for periodicreturn to the donor during the return cycle.

Processing containers associated with the system 150 include a container162 that holds anticoagulant for use during the procedure and acontainer 164 that holds saline solution for use in priming and purgingair from the system 150 before the procedure. The system furtherincludes collection containers 166 for receiving PC (and optionally PPP)for storage.

When the controller 154 operates the system 150 in the draw cycle, afirst branch 168 directs WB from needle 156 to the draw reservoir 158,in association with the draw pumping station 170 and a clamp 172. Anauxiliary branch 174 delivers anticoagulant to the WB flow inassociation with an anticoagulant pumping station 176.

A second branch 178 conveys the WB from the draw reservoir 158 to the WBinlet port 68 of the chosen processing chamber assembly 74/76, inassociation with the WB inlet pumping station 180. The draw pumpingstation 170 operates at a higher flow rate (at, for example, 100 ml/min)than the WB inlet pumping station 180, which operates continuously (at,for example, 50 ml/min).

The processing controller 154 includes a first scale 182 that monitorsthe weight volume of WB collected in the draw reservoir 158. The firstscale 182 intermittently operates the draw pumping station 170 tomaintain a desired weight volume of WB in the draw reservoir 158.

Once the desired volume of WB is present in the draw reservoir 158, theWB inlet pumping station 180 operates to continuously convey WB into thechosen processing chamber assembly 74/76.

The draw pumping station 170 continues to operate periodically duringthe draw cycle in response to the scale 182 to maintain the desiredweight volume of WB in the draw reservoir 158.

The WB enters the first stage chamber 84, where it is separated into RBCand PRP. This separation process has already been described.

A third branch 184, in association with the plasma pumping station 186,draws the PRP from the PRP collection port of the first processingchamber 84. The third branch 184 conveys the PRP to the PRP inlet port138 of the second processing chamber 86. There, the PRP is furtherseparated into PC and PPP. This separation process has already beendescribed.

As will be described in greater detail later, the processing controller154 monitors the location of the interface on the ramp 130 via theinterface controller 134. The controller 154 operates the plasma pumpingstation 186 to keep the maximum rate of the variable plasma pumpingstation 186 (for example, 25 ml/min) less than the WB inlet pumpingstation 180.

A fourth branch 188 conveys the RBC fro the RBC collection port 70 ofthe first stage processing chamber 84. The fourth branch 188 leads tothe return reservoir 160.

The processing controller 154 includes a second scale 190 that monitorsthe weight volume of RBC in the return reservoir 160. When a preselectedweight volume exists, the controller 154 shifts the operation of thesystem 150 from its draw cycle to its return cycle.

In the return cycle, the controller 154 stops the draw pumping station170 and starts a return pumping station 192. A fifth branch 194associated with the return pumping station 192 conveys RBC from thereturn reservoir 160 to the needle 156.

Meanwhile, while in the return cycle, the controller 154 keeps the WBinlet pumping station 180 and plasma pumping station 186 in operation tocontinuously process the WB pooled in the draw reservoir 158 through thefirst processing chamber 84.

During both draw and return cycles, PRP enters the PRP inlet port 138 ofthe second stage processing chamber 86. The PPP exits the PPP collectionport 136 of the second stage processing chamber through a sixth branch196 and into the return reservoir 160, joining the RBC there pooled.

Alternatively, by closing the clamp 198A and opening the clamp 198B, thePPP can be conveyed through a seventh branch 200 to one or morecollection containers 166.

After a procedure, the PC collected within the second processingcompartment 86 is transferred via the seventh branch 200 to one or morecollection containers 166 for storage.

B. Double Needle Platelet Collection System

The platelet collection system 152 shown in FIG. 28 employs two singlelumen phlebotomy needles 202A and 202B to obtain generally the sameprocessing results as the single needle system 150 shown in FIG. 27.Elements common to both systems 150 and 152 are assigned the samereference numeral.

The associated processing controller 154 operates the system 152 in acontinuous cycle, during which the donor's WB is continuously suppliedthrough the needle 202A to the chosen processing chamber assembly 74/76for separation into RBC, PC, and PPP, while RBC and PPP are continuouslyreturned to the donor through the needle 202B.

As in the single needle system 150, the harvested PC is retained forlong term storage. If desired, all or some PPP can be diverted from thedonor for storage.

As in the single needle system 150, the processing containers associatedwith the double needle system 152 include a container 162 that holdsanticoagulant and a container 164 that holds saline solution for use inpriming and purging air from the system 152.

The system 152 also includes similar collection containers 166 forreceiving PC (and optionally PPP) for storage.

Under the control of the controller 154, a first branch 204 directs WBfrom the needle 202A to the WB inlet port 68 of the first stageprocessing chamber 84, in association with the WB inlet pumping station206, which operates continuously at, for example, 50 ml/min. Anauxiliary branch 174 delivers anticoagulant to the WB flow inassociation with an anticoagulant pumping station 176.

The WB enters and fills the first processing chamber 84 in the mannerpreviously described, where centrifugal forces generated during rotationof the chosen chamber assembly 74/76 separate the WB into RBC and PRP.

A second branch 208, in association with the plasma pumping station 210,draws the PRP layer out the PRP collection port 72 of the first stageprocessing chamber 84, conveying the PRP to the PRP inlet port 138 ofthe second stage processing chamber 86, where it undergoes furtherseparation into PC and PPP.

The processing controller 154 monitors the location of the interface onthe ramp 130 and varies the speed of the plasma pumping station 210(using the interface controller 134, to be described later in greaterdetail) to keep the interface 26 at a prescribed location on the ramp130. As before described, the controller 154 keeps the maximum rate ofthe variable plasma pumping station 210 (for example, 25 ml/min) lessthan the WB inlet pumping station 206.

A third branch 212 conveys the RBC from the RBC collection port 70 ofthe first stage processing chamber 84. The third branch 212 leads to theneedle 202B.

The PPP exits the PPP collection port 136 of the second stage processingchamber 86 through a fourth branch 214, joining the third branch 212(carrying RBC) leading to the needle 202B. Alternatively, by closing theclamp 216A and opening the clamp 216B, the PPP can be conveyed through afifth branch 218 to one or more collection containers 166.

After a procedure, the PC collected within the second processingcompartment 86 is transferred via the fifth branch 218 to one or morecollection containers 166 for storage.

C. Enhancing Platelet Separation by Plasma Recirculation

Both single and double needle systems 150 and 152 (shown in FIGS. 27 and28 respectively) include a recirculation branch 220 and an associatedrecirculation pumping station 222. The processing controller 154 has arecirculation control system 224 that operates the pumping station 222to convey a portion of the PRP exiting the PRP collection port 72 of thefirst processing compartment 84 for remixing with the WB entering the WBinlet port 68 of the first processing compartment 84.

The control system 224 can control the recirculation of PRP in differentways.

As FIG. 29 shows, the recirculation control system 224 includes a sensor226 that senses the flow rate at which PRP exits the first processingcompartment 84, under the control of pumping station 186 (for the singleneed system 150) or pumping station 210 (for the double needle system152). As will be described in greater detail, this flow rate is itselfcontrolled by the interface controller 134.

The recirculation control system 224 employs a comparator 228 to comparethe sensed PRP flow rate to an established desired flow rate. If thesensed rate is less than the desired flow rate, the comparator 228 sendsa signal to increase rate at which the recirculation pumping station 222operates. And, if the sensed rate is more than the desired flow rate,the comparator 228 sends a signal to decrease the rate at which therecirculation pumping station 222 operates. In this way, the comparator228 maintains the PRP flow rate at the desired rate.

The desired PRP output rate is preselected to create within the firstcompartment 84 the processing conditions which maximize theconcentration of platelets in the PRP stream.

The desired rate of recirculation is based upon the radial flow rate ofplasma desired in the region where PRP is collected.

According to another aspect of the invention, the pumping rate of therecirculation pump 222 is maintained as a percentage (%RE) of thepumping rate of the whole blood inlet pump 180/206, governed as follows:

%RE=K*Hct−100

where:

Hct is the hematocrit of the donor's whole blood, measured beforedonation, and

K is a dilution factor that takes into account the volume ofanticoagulant and other dilution fluids (like saline) that are added tothe donor's whole blood before separation.

According to this aspect of the invention, the pumping rate of therecirculation pump 222 is maintained at the predetermined percentage(%RE) of the pumping rate of the whole blood inlet pump 180/206 tomaintain a surface hematocrit of about 30% to 35% in the entry regionRe. The preferred surface hematocrit in the entry region Re is believedto be about 32%.

Keeping the surface hematocrit in the entry region R_(e) in the desiredrange provides optimal separation of RBC from PRP, thereby optimizingthe radial flow of plasma in this region. If the surface hematocritexceeds the predetermined range, radial plasma flow in the entry regionR_(e) decreases. If the surface hematocrit falls below the predeterminedrange, the radial flow of PRP increases enough to sweep small RBC's andwhite blood cells into the PRP.

The value of the dilution factor K can vary according to operatingconditions. The inventor has determined that K=2.8, when ACDanticoagulant is added to constitute about 9% of the entry whole bloodvolume, and a saline dilution fluid is added in an amount representingabout 4% of donor body volume (i.e., 200 ml saline for 5000 ml in bodyvolume).

In an alternate arrangement (shown in phantom lines in FIG. 29), therecirculation control system 224 recirculates PPP, instead of PRP, basedupon %_(RE), as determined above.

In this arrangement, the system 224 uses a recirculation branch 230 andassociated pumping station 232 located downstream of the secondprocessing compartment 86. The comparator controls the pumping station232 in one of the same manners just described to mix PPP exiting thesecond compartment 86 with the incoming WB entering the firstcompartment 84.

By mixing PRP (or PPP) with the WB entering the first processingcompartment 84 to control surface hematocrit in the entry region R_(e),the velocity at which red blood cells settle toward the high-G wall 66in response to centrifugal force increases. This, in turn, increases theradial velocity at which plasma is displaced through the interface 26toward the low-G wall 64. The increased plasma velocities through theinterface 26 elute platelets from the interface 26. As a result, fewerplatelets settle on the interface 26.

EXAMPLE 2

A study evaluated a two stage separation chamber 74 like that shown inFIG. 16 in a platelet collection procedure on a healthy human donor. Thechamber 74 was part of a double needle system 152, like that shown in28. The system 152 recirculated PRP in the manner shown in FIG. 28 toobtain a hematocrit of 32.1% in the PRP collection region 124 of thechamber 74.

In this study, the low-G wall 64 of the first stage chamber 84 was nottapered in the direction of circumferential flow from the PRP collectionregion 124. The low-G wall 64 was isoradial along the circumferentialflow path in the first stage chamber 84, except for the presence of aRBC barrier 128, which stepped into the chamber across the RBCcollection passage, as shown in FIG. 17. The low-G wall 64 was isoradialalong the entire circumferential flow path of the second chamber 86.

FIG. 35A shows the platelet count sampled in the PRP (in 1000 plateletsper uL) over time during the 45 minute procedure. As there shown, aftera run time of 6 minutes, the platelet count was 173; after 10 minutes,the platelet count was 304; and after 20 minutes, the platelet countstabilized at 363.

FIG. 35B shows the physical size of the platelets collected in the PRPin terms of mean platelet volume (in femtoliters) sampled during theprocedure. As there shown, after a run time of 6 minutes, the meanplatelet size was 6.6; after 20 minutes, the mean platelet size rose to7.5; and at the end of the procedure, the mean platelet size was 8.2. Asize distribution study of the PC collected showed that about 3% of theplatelets collected were larger than 30 femtoliters (i.e., were verylarge platelets).

The platelet transfer efficiency in the first stage chamber 84 (i.e.,the percentage of available platelets entering the first stage chamber84 that were ultimately collected in the PRP) was 93.8%. In other words,the first stage chamber 84 failed to collect only 6.2% of the availableplatelets in the first stage chamber 84.

The platelet transfer efficiency in the second stage chamber 86 (i.e.,the percentage of available platelets in the PRP entering the secondstage chamber 86 that were ultimately collected as PC) was 99%. In otherwords, the second stage chamber 86 failed to collect only 1% of theplatelets present in the PRP in the second stage chamber 86.

The overall platelet collection efficiency of the chamber was about 81%,meaning that about 81% of the platelets in the whole blood processedwere ultimately collected. This is a significantly higher amount thanconventional processing can provide. In comparison, the comparableoverall platelet collection efficiency for two stage CS-3000® Centrifugechamber is about 50%.

This study demonstrates the increased separation efficiencies thatresult from chambers and systems that embody features of the invention.

EXAMPLE 3

Another study evaluated a two stage separation chamber like that inExample 2 in a platelet collection procedure on a healthy human donor.As in Example 2, a double needle system was used. The systemrecirculated PRP to obtain an inlet hematocrit of 34.3%.

In this study, the low-G wall 64 of the first stage chamber 84 wastapered in the direction of circumferential flow from the PRP collectionregion 124, like that shown in FIG. 17. The low-G wall 64 also includedRBC barrier 128 like that shown in FIG. 17. The low-G wall 64 was alsotapered along the entire circumferential flow path of the second chamber86.

FIG. 36A shows the platelet count sampled in the PRP (in 1000 plateletsper uL) over time during the 45 minute procedure. As there shown, aplatelet count of 300 was achieved in the first 5 minutes of theprocedure. The platelet count peaked at 331 after 21 minutes. At the endof the procedure, the platelet count was 302.

FIG. 36B shows the physical size of the platelets collected in the PRPin terms of mean platelet volume (in femtoliters) sampled during theprocedure. As there shown, after a run time of only 5 minutes, the meanplatelet size was 8.6, where it virtually remained throughout the restof the procedure. A size distribution study of the PC collected showedthat about 8.5% of the platelets collected were larger than 30femtoliters.

The second study also experienced greater collection efficiencies.

The platelet transfer efficiency in the first stage chamber 84 (i.e.,the percentage of available platelets that were ultimately collected inthe PRP) was 99.2%. In other words, the first stage chamber 84 failed tocollect less than 1% of the available platelets.

The platelet transfer efficiency in the second stage chamber 86 (i.e.,the percentage of available platelets in the PRP that were ultimatelycollected as PC) was 99.7%. In other words, the second stage chamber 86collected nearly all the platelets present in the PRP.

The overall platelet collection efficiency of the chamber was 85.3%.

This study further demonstrates the enhanced separation efficienciesthat the inventions can provide.

This study also shows the effect that the tapered low-G wall has infreeing greater number of platelets into the PRP stream. The effect isvirtually immediate. After only 5 minutes in the second study, theplatelet count was comparable to that encountered after 10 minutes inthe first study.

This study also demonstrates the effect that the tapered low-G wall hasin freeing larger platelets into the PRP stream. The effect, too, isvirtually immediate. After the first 5 minutes of the procedure, themean platelet size was comparable to that encountered after 30 minutesin the second study, which means that the larger platelets were alreadybeing collected. There were nearly 3 times more platelets of very largephysical size (i.e., over 30 femtoliters) collected in the second studythan in the first study.

IV. Interface Control Systems for the Enhanced Yield CircumferentialFlow Chambers

FIGS. 30 to 34 show the details of an alternative interface controlsystem 234, which can be used in association with either the single ordouble needle systems 150 or 152 previously described.

The interface control system 234 mounts the element that actually viewsthe interface on a rotating element of the centrifuge. The system 234relies upon a time pulse signal to determine the location of theinterface.

As FIGS. 30 and 31A/B show, the interface control system 234 includes alight source 236 mounted on the yoke 85 of the centrifuge 78. The source236 emits light that is absorbed by RBC. The control system 234 alsoincludes a light detector 244 mounted next to the light source 236 onthe yoke 85.

As FIG. 30 shows, a viewing head 238 carries both the light source 236and the light detector 244 for rotation on the yoke 85. As previouslydescribed, the yoke 85 rotates at a one omega speed, carrying theviewing head 238 with it. At the same time, the spool and bowlassemblies 80 and 82 carried by the yoke 85 rotate at a two omega speed.

In the illustrated and preferred embodiment, the viewing head 238 alsoserves as a counterweight for the umbilicus holder 106 that the yoke 85also carries (also see FIGS. 20 and 21).

In the illustrated and preferred embodiment, the light source 236includes a red light emitting diode. Of course, other colors, likegreen, could be used. In this arrangement, the light detector 244comprises a PIN diode detector.

An optical pathway 240 directs light from the source diode 236 out ontothe rotating bowl assembly 80 (see FIG. 31B). In the illustratedembodiment, the bowl assembly 80 is transparent to the light emitted bythe source diode 236 only in the region where the bowl assembly 80overlies the interface ramp 130.

The remainder of the bowl assembly 80 that lies in the path of theviewing head 238 carries a light reflecting material 243. Thisdifferentiates the reflective properties of the interface region of thebowl assembly 80 from those of the remainder of the bowl assembly 80.The material 243 could be light absorbing and serve the same purpose.

Alternatively, the source diode 236 could be gated on and off with thearrival and passage of the interface region of the bowl assembly 80relative to its line of sight.

The interface ramp 130 carried by the spool assembly 82 is made of alight transmissive material. The light from the source diode 236 willthus pass through the transparent region of the bowl assembly 80 and theramp 130 every time the rotating bowl assembly 80 and viewing head 238align.

The spool assembly 82 also carries a light reflective material 242 onits exterior surface behind the interface ramp 130 (see FIG. 36). Thematerial 242 reflects incoming light received from the source diode 236out through the transparent region of the bowl assembly 80. Theintensity of the reflected light represents the amount of light from thesource diode 236 that is not absorbed by the RBC portion of theinterface region.

The light detector 244 carried in the viewing head 238 receives thereflected light through an optical pathway. In the illustratedembodiment (see FIG. 31B), the optical pathway includes a lens 246, apenta prism 248, and an aperture 250.

In the illustrated embodiment, the lens 246 is about 9 mm in diameter,with the focal length of about 9 mm. In this arrangement, the lens 246forms a real image with a magnification of about three. Alternatively,the real image could be made smaller to provide a better depth of field.

The aperture 250 is preferably small (about 0.75 mm in diameter) toallow only a small portion of the real image to reach the detector 244.The preferred viewing field of the detector 244 is therefore small,i.e., preferably on the order of about 0.25 mm in diameter.

The system 234 further includes a data link 278 for transmitting lightintensity signals from the rotating viewing head 268 to an interfacecontrol circuit 270 on the stationary frame of the centrifuge. In theillustrated embodiment, the data link is optical in nature.Alternatively, slip rings could be used to transmit the light intensitysignals as voltage or current signals.

The optical data link 278 includes a second light source 254. The secondlight source 254 is carried within the confines of a hollow lightconduction passage 256 within the one omega drive shaft 257.

The optical data link 278 further includes a second light detector 268.The second detector 268 is carried on the non-rotating (i.e., zeroomega) base of the centrifuge below the hollow one omega drive shaft257. Light from the second light source 254 passes through the passage256 and a collimating sleeve 259 to fall upon the second detector 268.Like the first detector 244, the second detector 268 can comprise a PINdiode detector.

The second light source 254 comprises at least one red light emittingdiode carried within the passage 256 of the one omega shaft 257. Ofcourse, other colors, like green, could be used.

In the illustrated embodiment (see FIG. 30), the second light source 254includes three light emitting diodes 258 A/B/C arranged at 120 degreecircumferentially spaced intervals within the passage 256. Thisarrangement minimizes interference due to misalignment between thesecond light source 254 and the second detector 268. In an alternativearrangement, the light intensity signal from the second detector 268 canbe electronically filtered to eliminate interference signals caused bymisalignment.

The optical data link 278 also includes an intensity control circuit 252carried onboard the viewing head 238. The intensity control circuit 252adjusts the input to the source diode 236 so that the intensity of lighthitting the detector 244 remains constant.

The intensity control circuit 252 also connects the second light source254 in series to the first mentioned light source 236. Thus, as theintensity control circuit 252 adjust the input to the first light source236, it will also instantaneously adjust the input to the second lightsource 254. Thus the intensity of the light emitted by the source 254 isproportional to the intensity of light emitted by the source 236.

As FIG. 30 shows, the system 234 delivers electrical power to itsrotating components through wires 251. The same wires 251 deliver powerto the electric motor 253 that rotates the spool and bowl assemblies 80and 82.

FIG. 32 shows a representative embodiment for the intensity controlcircuit 252. As shown, the control circuit 252 includes a transistor 260that controls current flow to the series-connected first and secondlight sources 236 and 254.

The emitter of the transistor 260 is coupled to an amplifier 262. Oneamplifier input is coupled to the light detector 244 carried within theyoke viewing head 238. Another amplifier input is coupled to a referencediode 264. The circuit 252 also includes conventional current limitingresistors 266 to protect the light emitting diodes of the sources 236and 254.

As the intensity of light hitting the detector 244 decreases, the outputof the amplifier 262 increases. The transistor 260 conducts morecurrent. The intensities of the first and second light sources 236instantaneously increase by equal or otherwise proportional amounts.

Likewise, as the intensity of light hitting the detector 244 increases,the output of the amplifier 262 decreases. The transistor 260 conductsless current. The intensities of the first and second light sources 236instantaneously decrease by equal or proportional amounts.

As FIG. 33A shows, the interface control circuit 270 converts the sensedlight intensity output of the second detector 268 to amplified voltagesignals. A conventional waveshaping circuit converts the amplifiedvoltage signals to square wave time pulses.

From the time pulses, the interface control circuit 270 derives thephysical dimension of the interface (measured in inches). The interfacecontrol circuit 270 then generates a pump control signal based upon anydifferences between the derived interface dimension and a desiredinterface dimension.

As FIG. 33A shows, the first detector 244 will view fully reflectedlight, free of diminution at a fixed intensity I₁, during the period thereflective bowl material 243 and the viewing head 238 are in alignment.The second detector 268 will also view light at a fixed intensity I₂generated by the second light source 254 during this period.

As the transparent interface region of the bowl assembly 80 comes intoalignment with the viewing head 238, red blood cells displayed on theinterface ramp 130 will enter the optical path of the viewing head 238.

The red blood cells absorb the light from the first light source 236.This absorption reduces the previously viewed intensity of the reflectedlight. With decreasing light intensity sensed, the control circuit 252instantaneously increases the input to both first and second lightsources 236 and 254 to maintain a constant light intensity at the firstdetector 244.

Under the control of the circuit 252, both light sources 236 and 254will become brighter, assuming a new intensity level while the red bloodcell band of the interface pass past the viewing head 238.

As FIG. 33B shows, the first detector 244 will not sense this relativeincrease in intensity over time, because the control circuit 252instantaneously maintains the intensity I₁ viewed by the first detector244 constant. However, the second detector 268 will sense this relativeincrease in intensity I₂ over time.

As FIG. 33B shows, the second detector 268 generates an increasingintensity output signal I₂. The interface control circuit 270 convertsthe increasing intensity signal into the leading edge 274 of the squarepulse 272 shown in FIG. 38B. This event marks the beginning time (T₁) ofthe pulse 272.

Eventually, the intensity signal will stabilize, as the most denseregion of the red cell band of the interface enters the optical path ofthe viewing head 238. The interface control circuit 270 converts thestabilized intensity signal into the plateau 275 of the square pulse 272shown in FIG. 33B.

When the red cell band of the interface leaves the optical path of theviewing head 238, the first detector 244 will again view fully reflectedlight from the reflective bowl material 243. With increasing lightintensity sensed, the control circuit 252 will instantaneously decreasethe input to both first and second light sources 236 and 254 to maintaina constant light intensity at the first detector 244.

Again, the first detector 244 will not see this relative decrease inintensity over time, because the control circuit 252 instantaneouslymaintains the intensity I₁ viewed by the first detector 244 constant.However, the second detector 268 will sense this relative decrease inintensity over time. The second detector 268 generates a decreasingintensity output signal I₂. The interface control circuit 270 convertsthis signal to the trailing edge 276 of the square pulse 272 shown inFIG. 38B. This event marks the ending time (T₂) of the pulse 272.

As FIGS. 33A and B show, the interface control circuit 270 measures, foreach successive pulse 272A and 272B, the time period between the leadingpulse edge 274 (T₁ FIG. 33) and the trailing pulse edge 276 T₂ in FIG.33). This measurement (T₂ minus T₁) constitutes the length of the pulse(in seconds).

The interface control circuit 270 also preferably measures the timeperiod between two successive pulses (shown as 272A and 272B in FIG.33C). This period of time is measured between the leading edge 274 ofthe first pulse 272A (T₁ in FIG. 33C) and the leading edge 274 of thenext successive pulse 272B (T₃ in FIG. 33C). This measurementconstitutes the period of the adjacent pulses (in seconds).

After this measurement has been made, the interface control circuit 270then resets T₃ to T₁ for the next pulse measurement cycle (see FIG.34A).

As FIG. 34B shows, the interface control circuit 270 derives thephysical dimensions of the red cell band of the interface from thesetime pulse measurements, based upon the following relationship:$\frac{P_{L}}{P_{P}} = \frac{D_{I}}{D_{B}}$

where:

P_(L) is the measured length of the pulse (T₂ minus T₁) (in seconds);

P_(P) is the measured period of the pulse (T₃ minus T₁) (also inseconds);

D_(I) is the length of the red cell band of the interface (in inches) tobe derived; and

D_(B) is the circumference of the bowl assembly 80 (in inches).

If the rate of rotation of the bowl assembly 80 remains constant duringthe period of pulse measurements, the reciprocal of the frequency ofrotation in seconds (1/F_(rot), in Hz)) can be substituted for P_(P).

Based upon the above relationship, D_(I) can be derived as follows:$D_{I} = \frac{P_{L} \times D_{B}}{P_{P}}$

As FIG. 34B shows, the interface control circuit 270 compares thederived physical measurement of the interface D_(I) with a control value(D_(C)) to generate an error signal (E).

The interface control value D_(C) can comprise a preselected fixedabsolute value (in inches) that the user inputs. Alternatively, theinterface control value D_(C) can be expressed as a percentage basedupon the length of the interface ramp 130 (i.e., red cells should occupyno more than 30% of the interface ramp 130).

With reference now also to FIG. 25A, if the error signal (E) ispositive, indicating that the red cell band of the interface is toolarge, the interface control circuit 270 generates a signal to reducethe pumping rate of the plasma pumping station 186/210 (see FIG. 34B).This pushes the RBC region away from the PRP collection port 72 backtoward the desired control position (FIG. 25B), where the error signal(E) is zero.

With reference to FIG. 25C, if the error signal (E) is negative,indicating that the red cell band of the interface is too small, theinterface control circuit 270 generates a signal to increase the pumpingrate of the plasma pumping station 186/210 (see FIG. 34B). This pushesthe RBC region toward the PRP collection port 72 back toward the desiredcontrol position (FIG. 25B), where the error signal (E) is again zero.

The optical data link 278 described above is representative of a broaderclass of systems for transmitting a control signal between a rotatingelement and a stationary element without mechanical contact between thetwo elements.

Like the illustrated optical data link 278, such a system employs sensormeans on either the rotating or stationary element. The sensor meanssenses an operating condition that is subject to change. The sensormeans generates a first output signal that varies according to changesin the sensed operating condition.

Like the illustrated optical data link 278, such a system includes anenergy emitter on the one element that carries the sensor means. Theemitter emits energy to the other element without mechanical contactwith the other element. The emitter modulates the emitted energyaccording to variations occurring in the intensity of the first outputsignal. Alternatively, the sensor means itself can constitute an emitterof modulated energy.

The emitted energy used by the data link 278 is light. However, soundenergy or other types of electromagnetic energy could be used as well.

Like the illustrated data link 278, the system includes a detector onthe other element for receiving the modulated energy emitted by theemitter. The detector demodulates the detected energy to generate asecond output signal that, like the first output signal, variesaccording to the changes in the sensed operating condition.

Such a “connectionless” system for transmitting data between moving andstationary elements would be applicable for use for all sorts of realtime control functions, not just interface control.

Various features of the inventions are set forth in the followingclaims.

I claim:
 1. A chamber for rotation about an axis to separate a bloodsubstance into its components comprising a separation zone including alow-G side wall radially spaced from the axis, a high-G wall radiallyspaced from the axis farther than the low-G side wall, end walls spacedapart circumferentially about the axis, the separation zone having a topand a bottom, an inlet port located above the bottom of the separationzone to introduce the blood substance into the separation zone along apath that is oriented generally parallel to the axis of rotation forconveyance in a generally circumferentially flow path about the axis forseparation into its component parts, a collection passage to receive ablood component that is separated in the separation zone, the collectionpassage being axially spaced below the bottom of the separation zone andincluding an entrance in the bottom of the separation zonecircumferentially spaced from the inlet port to define a path that isoriented generally parallel to the axis of rotation for conveying theseparated blood component from the separation zone and into thecollection passage, whereby, during rotation, first and secondcircumferentially spaced non-turbulent vortex regions are produced thatare mutually aligned parallel to the axis of rotation, the firstnon-turbulent vortex region extending from the inlet port longitudinallyacross the circumferential flow path, and the second non-turbulentvortex region extending from the entrance of the collection passagelongitudinally across the circumferential flow path.
 2. A chamberaccording to claim 1 wherein the inlet port is in the top of theseparation zone.
 3. A chamber according to claim 1 including an outletport to convey at least one of the separated components from theseparation zone along a path that extends generally parallel to the axisof rotation.
 4. A method for separating a blood substance into itscomponents comprising the steps of forming a separation chamber having aseparation zone including a low-G side wall radially spaced from an axisof rotation, a high-G wall radially spaced from the axis farther thanthe low-G side wall, end walls spaced apart circumferentially about theaxis, the separation chamber having a top and a bottom, the separationchamber further having a collection passage to receive a blood componentthat is separated in the separation zone, the collection passage beingaxially spaced below the bottom of the separation zone and including anentrance in the bottom of the separation zone circumferentially spacedfrom the inlet port, rotating the separation chamber, while rotating theseparation chamber, introducing the blood substance into the separationzone through an inlet port that is located above the bottom along a paththat is oriented generally parallel to the axis of rotation forconveyance in a generally circumferentially flow path about the axis forseparation into its component parts, thereby forming a firstnon-turbulent vortex region that extends from the inlet port generallyparallel to the axis of rotation longitudinally across thecircumferential flow path, and while rotating the separation chamber,conveying the separated blood component from the separation zone andinto the collection passage through the entrance, thereby forming asecond non-turbulent vortex region that extends from the entrancegenerally parallel to the axis of rotation longitudinally across thecircumferential flow path and being circumferentially spaced from thefirst non-turbulent vortex region.